71 research outputs found
Assay of healthful properties of wild blackberry and elderberry fruits grown in Mediterranean area
No full textBerry fruits consumption is associated with the prevention of most illness, such as cardiovascular diseases, cancer and obesity. Moreover, these berries can modify the post-prandial glycemic response, through the inhibition of the enzymes responsible for carbohydrates hydrolysis: α-amylase and α-glucosidase. In this study we evaluated wild blackberry and elderberry fruits grown in the Mediterranean area, in terms of healthy composites, in particular phenolic compounds. Our results showed a high variability in the concentration of phytochemicals, with higher values in elderberry than in blackberry extracts. Total phenolic content ranged between 635.24–1336.28 mg gallic acid equivalents/100 g fw for blackberries and between 391.46and 811.65 mg gallic acid/100 g fw for elderberries whereas total flavonoids content ranged between 1738 and 4971 mg quercetin/100 g fw and 1136–3174 mg quercetin/100 g fw for blackberries and elderberries, respectively. Results indicated that wild blackberry and elderberry fruits represent a natural source of antioxidant compounds, besides having a potential inhibitory effect against α-glucosidase (27.67% inhibition and 28.27% for blackberries and elderberries, respectively) and α-amylase, providing a support for patients with mellitus diabetes. Anyway, future investigations based on clinical trials are required in order to prove the healthful effects of health promoting compounds on diabetic patients
Degradation of EEG microstates patterns in subjective cognitive decline and mild cognitive impairment: Early biomarkers along the Alzheimer's Disease continuum?
No full textAlzheimer's disease (AD) pathological changes may begin up to decades earlier than the appearance of the first symptoms of cognitive decline. Subjective cognitive decline (SCD) could be the first pre-clinical sign of possible AD, which might be followed by mild cognitive impairment (MCI), the initial stage of clinical cognitive decline. However, the neural correlates of these prodromic stages are not completely clear yet. Recent studies suggest that EEG analysis tools characterizing the cortical activity as a whole, such as microstates and cortical regions connectivity, might support a characterization of SCD and MCI conditions. Here we test this approach by performing a broad set of analyses to identify the prominent EEG markers differentiating SCD (n = 57), MCI (n = 46) and healthy control subjects (HC, n = 19). We found that the salient differences were in the temporal structure of the microstates patterns, with MCI being associated with less complex sequences due to the altered transition probability, frequency and duration of canonic microstate C. Spectral content of EEG, network connectivity, and spatial arrangement of microstates were instead largely similar in the three groups. Interestingly, comparing properties of EEG microstates in different cerebrospinal fluid (CSF) biomarkers profiles, we found that canonic microstate C displayed significant differences in topography in AD-like profile. These results show that the progression of dementia might be associated with a degradation of the cortical organization captured by microstates analysis, and that this leads to altered transitions between cortical states. Overall, our approach paves the way for the use of non-invasive EEG recordings in the identification of possible biomarkers of progression to AD from its prodromal states
Ricerca del bosone di Higgs in produzione associata col bosone vettore W, nello stato finale WH->(munu) (tautau -> mu + tau-jet + 3nu), all'esperimento CMS a LHC
No full textIl Modello Standard (MS) è la teoria scientifica più dibattuta degli ultimi anni nel mondo della fisica delle alte energie. Essa racchiude i fondamenti della materia e descrive le interazioni che regolano l'universo. Il MS è stato confermato in numerosi esperimenti, quali LEP e Tevatron, ma presenta ancora un ultimo interrogativo relativo all'origine della massa delle particelle. Il MS cerca di spiegare ciò tramite il meccanismo di Higgs, proposto da Peter Higgs nel 1964 \cite{Higgs}: viene introdotta una nuova particella, chiamata \emph{bosone di Higgs}, che ha lo scopo tramite il suddetto meccanismo di fornire massa alle particelle. Di tale particella non si conosce la massa, che viene infatti assunta come parametro libero della teoria.
Scopo di tale lavoro di tesi è stato quello di studiare presso l'esperimento CMS (\emph{Compact Muon Solenoid}) a LHC (\emph{Large Hadron Collider}) il canale di produzione associata WH, nell'intervallo di massa 115 GeV/ 135 GeV/, negli stati finali
in cui uno dei provenienti dall'Higgs decade in muone e l'altro decade in adroni ().
Visti i risultati di Dicembre 2011 \cite{limiteCMS} , la ricerca del bosone di Higgs è ormai concentrata nell'intervallo a bassa massa. Nonostante in questa regione il processo di produzione dominante sia la \emph{gluon-gluon fusion}, il canale investigato risulta favorito per la presenza del proveniente dal bosone vettore che viene utilizzato come \emph{trigger}, in modo tale da ottenere una migliore segnatura dell'evento, grazie alle eccellenti prestazioni dell'esperimento CMS, in particolare delle camere a muoni.
Il canale di decadimento scelto è , che, nell'intervallo di massa considerato, ha un BR inferiore al 10\% e viene dopo il decadimento dominante in . La richiesta di tale segnatura è stata dettata dal fatto che il decadimento in favorisce la reiezione del fondo di QCD, che nel caso del decadimento in quark risulta molto complicato.
Anche se questo canale risulta molto interessante, la sua bassa sezione d'urto di produzione (0.75 pb) rende necessario lo studio accurato dei fondi principali, quali i processi \emph{Drell-Yan}, \emph{W+jets}, e dei fondi irriducibili , e .
Lo scopo principale di tale lavoro di tesi è stato quello di applicare e ottimizzare diversi criteri di selezione sugli oggetti ricostruiti per poter controllare questi fondi. Inoltre sono stati studiati una serie di tagli topologici per poter mantenere un accordo tra i dati reali e le simulazioni Monte Carlo, studiando ad esempio le cariche dei tre leptoni nello stato finale e richiedendo che non ci siano altri oggetti nell'evento.
In tale lavoro di tesi è stata analizzata tutta la statistica del 2011 raccolta da CMS, ovvero circa 4.7 fb.
Inoltre per verificare che la selezione applicata fosse coerente con quanto ci si aspettava, sul segnale è stata applicata una tecnica di \emph{truth-matching}, in cui sono stati confrontati gli oggetti a livello di verità Monte Carlo e quelli ricostruiti dopo il passaggio nel rivelatore e l'applicazione di algoritmi di ricostruzione. Tale procedura è stata utilizzata per comprendere la purezza del campione di segnale e per migliorare la selezione applicata.
Nell'ultima fase ci si è concentrati maggiormente sullo studio dei fondi, utilizzando non le simulazioni Monte Carlo, ma direttamente i dati. \`E stata applicata la tecnica del \emph{fake-rate}: per molte analisi con leptoni nello stato finale una delle più rilevanti sorgenti di fondo è data dalla possibilità che uno o più \emph{jet} vengano scambiati per leptoni. Questi processi non vengono sempre ben descritti da simulazioni Monte Carlo e quindi spesso si preferisce usare dei metodi, cosiddetti \emph{Data - Driven}, in cui vengono utilizzati direttamente i dati per una corretta predizione del fondo.
Questo studio ha migliorato l'accordo con i dati reali, ha confermato la correttezza delle richieste effettuate sugli oggetti nello stato finale e ha permesso di valutare l'affidabilità delle simulazioni Monte Carlo
Structural results on circular-arc graphs and circle graphs: A survey and the main open problems
No full textArtículo de publicación ISICircular-arc graphs are the intersection graphs of open arcs on a circle. Circle graphs are
the intersection graphs of chords on a circle. These graph classes have been the subject
of much study for many years and numerous interesting results have been reported.
Many subclasses of both circular-arc graphs and circle graphs have been defined and
different characterizations formulated. In this survey, we summarize the most important
structural results related to circular-arc graphs and circle graphs and present the main open
problems.The first author was partially supported by FONDECyT Grant 1110797 and Millennium Science Institute ‘‘Complex
Engineering Systems’’ (Chile). All the authors were partially supported by ANPCyT PICT-2007-00518, UBACyT Grant
20020090300094 and CONICET PIP 112-200901-00160 (Argentina)
Microenvironmental and metabolic influences in tumor cell redox homeostasis
No full textRedox reactions dictate protein shape, regulate enzyme activity, and underscore cellular metabolism. When redox poise fails and cells are overcome by oxidation, cellular death soon follows. Redox biology is an especially important aspect of cancer cell biology, because oncogene-induced hyperproliferation results in pro-oxidant tumor cell phenotypes. Thus, tumor cell antioxidant systems are often inherently strained and vulnerable to further oxidative attack. Targeted therapies can be designed to kill tumor cells by pushing them beyond redox thresholds compatible with cellular life without injuring healthy cells that can more effectively dissipate oxidative stress. Radiation therapy and many chemotherapeutic drugs use this mechanism of oxidant-based cell killing to eliminate tumor cell populations. However, in clinical settings, these therapies face tumor cell resistance stemming from multifactorial changes in cellular drug and energy metabolism, environmental selective pressures, and intratumoral heterogeneity. To further advance efficacious and selective anticancer strategies, increased understanding of microenvironmental and metabolic influences in tumor cells redox homeostasis is needed.
Poorly arranged and malfunctioning vasculature in the tumor microenvironment causes heterogeneous regions of hypoxia to form throughout the solid mass. Clinically, tumor hypoxia is a negative prognostic indicator for a more aggressive phenotype and is associated with treatment resistance. Metabolically, tumor hypoxia results in hypoxia inducible factor-driven gene network activation and enhanced mitochondrial production of reactive oxygen species. Given this, it is important to match laboratory in vitro studies as closely as possible to the in vivo conditions of the tumor microenvironment. However, even simple in vitro hypoxic studies are complicated by the rigors of hypoxic experimentation and, thus, most studies are conducted at hyperoxic atmospheric levels of oxygen. Engineered microfluidic platforms offer an approach to hypoxic laboratory studies. This report validates an ease-of-use platform suitable to study complex cell behaviors in hypoxia. Herein we present the design and implementation of an open-well microfluidic platform that enables on-chip cell culture, experimentation, and microscopy in a controlled hypoxic microenvironment. This platform has been theoretically and experimentally validated to quickly induce and maintain 0.3 mg/L O2 hypoxia, and it has enabled studies of the stabilization of hypoxia inducible factor in hypoxia and the redox response of the mitochondrial matrix in hypoxia.
The glutathione system functions in antioxidant defense and xenobiotic detoxification to preserve subcellular redox poise and maintain enzymes in functional reduced states. Glutathione is produced from its constitutive amino acids in a two-step enzymatic process that occurs in the cytosol. Despite glutathione’s role in cellular antioxidant defense, its production in the pro-oxidant state of hypoxia has been under studied. We investigated whether glutathione production in hypoxia differed by cellular transformation state and malignancy in an isogenic series of breast cancer cells. Unexpectedly, we observed a glutathione biosynthetic gene downregulation and a loss of glutathione content following culture in chronic mild hypoxia. This result did not differ with transformation state and was seen over a range of hypoxic exposures. With further investigation of glutathione synthesis in hypoxia, strategies may be uncovered to specifically promote the loss of glutathione content by cancer cells in the hypoxic tumor microenvironment.
Increased glutamine uptake and turnover contributes to the metabolic reprogramming of transformed cells. Oncogenic glutaminolysis results in glutamine utilization that far exceeds the anabolic needs of transformed cells for nitrogen and increases the anaplerotic flux of glutamine through the TCA cycle to support mitochondrial respiration. MYC and RAS-transformed tumor cells are particularly reliant on glutamine metabolism for cellular homeostasis. In these cells, glutaminolysis promotes rapid cellular proliferation by supporting energy generation, cell division, and antioxidant defense.
Herein we report an investigation of the metabolic requirements of tumor cells for glutamine to preserve glutathione redox homeostasis. Glutamine is deaminated by glutaminase to glutamate, a TCA cycle carbon that supports mitochondrial energy generation via oxidative phosphorylation and serves as a direct substrate for cytosolic glutathione synthesis. Cytosolic and mitochondrial glutathione pools are distinctly regulated and maintained at independent concentrations. RAS-transformed tumor cells expressing the Glrx-roGFP2 redox biosensor, a GFP-based subcellular probe sensitive to local glutathione redox potentials, were exposed to glutamine deprivation and pharmacologic inhibition of glutaminolytic enzymes. We found that oncogenic RAS increases cellular reliance on glutamine to maintain glutathione redox poise. Furthermore, we report that cytosolic glutathione homeostasis is more independent of glutamine metabolism and far more robust in resisting changes to baseline redox potential than mitochondrial matrix glutathione. The mitochondrial matrix requires transaminase-mediated glutamine metabolism to resist glutathione oxidation. Alpha-ketoglutarate, a TCA cycle carbon and downstream metabolite of glutamate, can prevent mitochondrial glutathione oxidation and aid GSH biosynthesis during glutamine deprivation. However, alpha-ketoglutarate cannot restore proliferation to glutamine-deprived KRAS-transformed tumor cells that require transaminase-mediated glutamine metabolism for rapid proliferation.
This study demonstrates that glutaminolysis is needed to maintain glutathione concentrations and mitochondria glutathione redox poise in RAS-transformed cells. Tumor cell reliance on glutamine for mitochondrial redox homeostasis may present targets for the rational design of novel or companion approaches to selectively predispose cancer cells to pathologic oxidation in anticancer therapies.
The dissertation research presented herein explores cancer redox biology from a number of vantage points. The Glrx-roGFP2 redox biosensor enabled unique examination of glutathione redox responses to physical, xenobiotic, and metabolic insults to live cancer cells in real time. It is hoped that these studies of the microenvironmental and metabolic influences in tumor cell redox homeostasis contribute to the body of knowledge that is drawn upon to advance cancer treatment.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-05-01The student, Matthew Leslie, accepted the attached license on 2017-08-07 at 14:49.The student, Matthew Leslie, submitted this Dissertation for approval on 2017-08-08 at 11:19.This Dissertation was approved for publication on 2017-08-10 at 08:56.DSpace SAF Submission Ingestion Package generated from Vireo submission #11591 on 2018-08-31 at 17:16:30Made available in DSpace on 2018-09-04T20:33:44Z (GMT). No. of bitstreams: 2
LESLIE-DISSERTATION-2018.pdf: 9551171 bytes, checksum: fe75a096ed35e197dc2a7810df411dca (MD5)
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Event-related potential markers of subjective cognitive decline and mild cognitive impairment during a sustained visuo-attentive task
No full textSubjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease stages lack well-defined electrophysiological correlates, creating a critical gap in the identification of robust biomarkers for early diagnosis and intervention. In this study, we analysed event-related potentials (ERPs) recorded during a sustained visual attention task in a cohort of 178 individuals (119 SCD, 40 MCI, and 19 healthy subjects, HS) to investigate sensory and cognitive processing alterations associated with these conditions. SCD patients exhibited significant attenuation in both sensory (P1, N1, P2) and cognitive (P300, P600, P900) components compared to HS, with cognitive components showing performance-related gains. In contrast, MCI patients did not show a further decrease in any ERP component compared to SCD. Instead, they exhibited compensatory enhancements, reversing the downward trend observed in SCD. This compensation resulted in a non-monotonic pattern of ERP alterations across clinical conditions, suggesting that MCI patients engage neural mechanisms to counterbalance sensory and cognitive deficits. These findings support the use of electrophysiological markers in support of medical decision-making, enhancing personalized prognosis and guiding targeted interventions in cognitive decline
Author Correction: A portrait of the Higgs boson by the CMS experiment ten years after the discovery
No full textIn the version of this article initially published, CMS Collaboration author names, affiliations and acknowledgements were omitted and have now been included in the HTML and PDF versions of the articl
Predictors of function, activity, and participation of stroke patients undergoing intensive rehabilitation: a multicenter prospective observational study protocol
No full textBackground: The complex nature of stroke sequelae, the heterogeneity in rehabilitation pathways, and the lack of validated prediction models of rehabilitation outcomes challenge stroke rehabilitation quality assessment and clinical research. An integrated care pathway (ICP), defining a reproducible rehabilitation assessment and process, may provide a structured frame within investigated outcomes and individual predictors of response to treatment, including neurophysiological and neurogenetic biomarkers. Predictors may differ for different interventions, suggesting clues to personalize and optimize rehabilitation. To date, a large representative Italian cohort study focusing on individual variability of response to an evidence-based ICP is lacking, and predictors of individual response to rehabilitation are largely unexplored. This paper describes a multicenter study protocol to prospectively investigate outcomes and predictors of response to an evidence-based ICP in a large Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation.Methods: All patients with diagnosis of ischemic or hemorrhagic stroke confirmed both by clinical and brain imaging evaluation, admitted to four intensive rehabilitation units (adopting the same stroke rehabilitation ICP) within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled (expected sample: 270 patients). Measures will be taken at admission (T0), at discharge (T1), and at follow-up 6 months after a stroke (T2), including clinical data, nutritional, functional, neurological, and neuropsychological measures, electroencephalography and motor evoked potentials, and analysis of neurogenetic biomarkers.Statistics: In addition to classical multivariate logistic regression analysis, advanced machine learning algorithms will be cross-validated to achieve data-driven prognosis prediction models.Discussion: By identifying data-driven prognosis prediction models in stroke rehabilitation, this study might contribute to the development of patient-oriented therapy and to optimize rehabilitation outcomes
PRedicting the EVolution of SubjectIvE Cognitive Decline to Alzheimer’s Disease With machine learning: the PREVIEW study protocol
No full textDegradation of EEG microstates patterns in subjective cognitive decline and mild cognitive impairment: Early biomarkers along the Alzheimer’s Disease continuum?
No full text- …
